Glycine vs Melatonin

Mechanism

Glycine is the simplest amino acid with profound neurological and metabolic roles. It is an inhibitory neurotransmitter acting at glycine receptors (strychnine-sensitive) in the brainstem and spinal cord, inducing a drop in core body temperature that facilitates sleep onset. It is also an obligatory co-agonist at the NMDA receptor glycine binding site, modulating excitatory neurotransmission. Metabolically, glycine is the rate-limiting amino acid for glutathione synthesis (glutathione = glycine + cysteine + glutamate), a key substrate for collagen synthesis (every 3rd amino acid), essential for creatine synthesis, bile acid conjugation, heme synthesis, and one-carbon metabolism.

Standard Dosing

3-5g daily

Timing

3g before bed for sleep (core body temperature reduction). Divided doses during day for glutathione support. Powder in water has a mildly sweet taste.

Cycle Duration

ongoing

Side Effects

• Mild drowsiness
• Soft stools at high doses
• Nausea (rare)
• Generally extremely well-tolerated

Contraindications

• Very few absolute contraindications. Caution in severe renal disease.

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Mechanism

Melatonin (N-acetyl-5-methoxytryptamine) is synthesized from serotonin in the pineal gland, regulated by the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract. It binds MT1 and MT2 G-protein coupled receptors: MT1 activation suppresses neuronal firing in the SCN (sleep onset), while MT2 modulates circadian phase shifting. Beyond sleep, melatonin is a potent antioxidant that scavenges hydroxyl radicals, peroxynitrite, and singlet oxygen, and upregulates antioxidant enzymes (GPx, SOD, catalase) via Nrf2. It has anti-inflammatory properties (NF-kB suppression), immunomodulatory effects, oncostatic activity (anti-proliferative in several cancer types), and mitochondrial protective functions.

Standard Dosing

0.3-1mg for sleep onset (physiological); 3-5mg for jet lag; 10-20mg for oncological adjunct (under supervision)

Timing

30-60 minutes before desired sleep onset. For circadian phase advance: 4-6 hours before desired bedtime. Sublingual for faster onset. Dim lights 1-2 hours before taking.

Cycle Duration

Short-term for jet lag (3-5 days); ongoing at low dose for circadian support if needed; extended for oncological use under supervision

Side Effects

• Morning grogginess (dose too high)
• Vivid dreams/nightmares
• Headache
• Nausea
• Dizziness
• Reduced libido (at high chronic doses)
• Next-day drowsiness
• Depression (rare)

Contraindications

• Autoimmune conditions (immunostimulatory)
• Depression (may worsen in some individuals)
• Seizure disorders (mixed data)
• Pregnancy/lactation

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